Pipecolic Acid → 2-(4-chloro-2-fluoro-5-isopropoxyphenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine-1,3(2H,8aH)-dione

HRID 1903643Notes

Reaction equation

HRID 1903643 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH:9]([CH3:11])[CH3:10])=[CH:6][C:5]([N:12]=[C:13]=[O:14])=[C:4]([F:15])[CH:3]=1.[OH-].[Na+].[NH:18]1[CH2:26][CH2:25][CH2:24][CH2:23][CH:19]1[C:20](O)=[O:21]>ClC1C=CC=CC=1>[Cl:1][C:2]1[C:7]([O:8][CH:9]([CH3:10])[CH3:11])=[CH:6][C:5]([N:12]2[C:20](=[O:21])[CH:19]3[CH2:23][CH2:24][CH2:25][CH2:26][N:18]3[C:13]2=[O:14])=[C:4]([F:15])[CH:3]=1

Participants

5

Reactant 3

HCID 849Pipecolic AcidHCID 14798Sodium HydroxideHCID 132729244-Chloro-2-fluoro-5-isopropoxyphenyl isocyanate

Product 1

HCID 132812152-(4-chloro-2-fluoro-5-isopropoxyphenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine-1,3(2H,8aH)-dioneYield 17.6%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 4-chloro-2-fluoro-5-isopropoxyphenyl isocyanate (2.3 g) in chlorobenzene (10 ml) was added to a 2% aqueous solution of sodium hydroxide (25 ml) containing pipecolic acid (1.3 g), and the mixture was stirred at room temperature (ca. 20° C.) for 3 hours. After allowed to stand overnight, the precipitated crystals were collected by filtration and washed with ether. The crystals were combined with water (20 ml) and adjusted to pH 2 or less with hydrochloric acid, followed by reflux for 3 hours. After allowed to cool, the mixture was extracted with ether, dried and concentrated. The residue was purified by silica gel chromatography to give 0.6 g of 2-(4-chloro-2-fluoro-5-isopropoxyphenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine-1,3(2H,8aH)-dione (Compound No. 7). M.P. 60.5°-64.5° C.

Workup

  1. waitto stand overnight
  2. filtrationthe precipitated crystals were collected by filtration
  3. washwashed with ether
  4. temperatureby reflux for 3 hours
  5. temperatureto cool
  6. extractionthe mixture was extracted with ether
  7. customdried
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-606e09dbdb0841469e61d485e6867324
Source dataset
uspto-grants-1984_03
Patent number
US04437877

Reaction notes

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